DOCSLIB.ORG

Nontuberculous Mycobacteria and the Environment (Insights from Hawai’I)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Nontuberculous Mycobacteria and the Environment (Insights from Hawai’I) Nontuberculous mycobacteria and the environment (insights from Hawai’i) Jennifer R. Honda, PhD 23rd Annual Conference of the Union-North America Region Post-Graduate Course 2-20-19 What’s the myco difference? Mycobacterium tuberculosis (M.tb) Nontuberculous mycobacteria (NTM) Lung, intracellular Ubiquitous environmental distribution Typical place of residence: Mycobacterium abscessus species M. gordonae Mycobacterium avium complex (MAC) M. terrae M. avium M. gilvum Pathogenicity M. intracellulare M. smegmatis ruler: M. chimaera 10 9 8 7 6 5 4 3 2 1 Causes TRUE lung disease Opportunistic pathogens Rarely causes lung disease Overall available knowledge: NTM lung disease • General population are constantly exposed, but infection is rare. • Most common of the ”rare lung diseases.” • General population: 4-7/100,000 persons • Elderly (>65yr) 15-47/100,000 persons • Outbreaks of NTM have occurred. • Treatment is inadequate, lengthy, and expensive. • Person-to-person transmission is not known to occur, but may occur in patients with cystic fibrosis in close proximity to infected persons. Why do we care about NTM lung disease? Changing prevalence of NTM and TB in the U.S. Inadequate knowledge NTM TB Zheng, et al. Q J Med, 2013 • In the U.S., nearly 180,000 individuals are infected with NTM. Major mycobacterial lipids • Prevalence is increasing at >8.2% annually. Tran, T. et al, Tubercu J, 2019; under review Contributing host and environmental factors Virulence of NTM Most HOST-RISK FACTORS Least ANATOMIC ENVIRONMENTAL Prior bronchiectasis EXPOSURE Emphysema Aerosolized water (hot tubs, Pneumoconiosis showerheads) Chronic aspiration Aerosolized soil exposure Calcified chest adenopathy Residence in Southeast U.S. and IMMUNOLOGIC-GENETIC Hawai’i Cystic fibrosis, CFTR anomalies Alpha-1-antitrypsin anomalies Pulmonary alveolar proteinosis Partial deficiency in IFNg(?) TNFa antagonists* Inhaled corticosteroids Multigenic disorder Completely normal hosts Ciliary defect (MST1R) (size of inoculum matters?) Host-susceptible phenotype of unknown cause Slender individuals with Marfanoid body habitus (scoliosis, pectus excavatum, mitral valve prolapse) Honda et al Clinical Handbook on NTM, 2017. M. MARSEILLENSE M. LLATZERENSE M. MONACENSE M. MALMOENSE M. MUCOGENICUM What are the most common NTM species M. MARINUM M. NEBRASKENSE M. YONGONENSE M. NEOAURUM identified in patient respiratory specimens M. ALVEI M. NONCHROMOGENICUM M. ARUPENSE M. NOVOCASTRENSE at National Jewish Health? M. ASIATICUM M. OBUENSE M. BOUCHEDURHONENSE M. PALUSTRE M. CELATUM M. PARAENSE Mycobacterial Clinical Labs M. CHLOROPHENOLICUM M. PARAFFINICUM U.S. NTM isolates (7/2013-7/2015) M. COLOMBIENSE M. PARASCROFULACEUM M. CONCEPTIONENSE M. PEREGRINUM M. CONSPICUUM M. PHLEI Of 3,096 NJH isolates, these are the top 7: M. COOKII M. PHOCAICUM M. COSMETICUM M. PORCINUM (66%) M. ELEPHANTIS M. SASKATCHEWANENSE M. EUROPAEUM M. SCROFULACEUM 15.83% M. ABSCESSUS M. FARCINOGENES M. SENEGALENSE M. FREDERIKSBERGENSE M. SENUENSE 12.63% M. AVIUM M. GASTRI M. SEPTICUM 9.01% M. FORTUITUM M. GENAVENSE M. SETENSE Total=100% M. GOODII M. SHERRISII 8.91% M. INTRACELLULARE M. GORDONAE M. SIMIAE 8.85% M. MASSILIENSE M. HAEMOPHILUM M. SMEGMATIS M. HASSIACUM M. STOMATEPIAE 5.46% M. CHELONAE M. HECKESHORNENSE M. SZULGAI M. HIBERNIAE M. TERRAE M. HODLERI M. THERMORESISTIBLE M. IMMUNNOGENUM 5.33% M. CHIMAERA M. TIMONENSE * M. INTERJECTUM M. TRIPLEX M. IRANICUM M. TRIVIALE M. KANSASII M. WOLINSKYI M. KUBICAE M. XENOPI M. KUMAMOTONENSE M. LENTIFLAVUM M. LITORALE How are infections acquired? Inhalation of NTM aerosolized from environmental sources Drinking water Heater-cooler Heater-cooler distribution units Drinking water units distribution systems Animals Animals Faucets, ice systems Faucets, ice machines machines Acidic, brown Water tanks Acidic, brown Water tanks water swamps water swamps Hot tubs/spas Hot tubs/spas Showerheads Soil Soil Showerheads Forest soil and Boreal forest soil peats and peats Studies have reported NTM in a variety of different geographic locations. But NTM diversity has never been comprehensively characterized in a single, large geographic area. e.g., Asia, Europe, Africa, U.S. Environmental NTM Biofilms • U.S. showerheads are enriched for NTM (Feazel, 2009). • Identical NTM fingerprints from the NTM isolates from patient lungs and their matched shower water isolates (Falkinham, 2008; 2011). • Showerhead biofilms are the most frequently sampled environmental sources to describe the presence of environmental NTM globally. Mycobacterium Cut open shower hoses reveal diverse biofilms Shower hose biofilms Proctor, et al Water Research, 2018 Soto-Giron, AEM 2016 Showerhead Microbiome and NTM Lung Disease Showerhead Microbiome Project (Gerbert et al, mBio, 2018) Hawai’i is a U.S. Hot Spot for NTM Lung Disease • A 1979 survey of public health laboratories showed Hawai’i had the highest M. avium complex isolation rate in the U.S. (Good, 1980). • Hawai’i has the highest prevalence - 396 cases/100,000 population among persons > 65 years-old (1997-2007). (Adjemian, AJRCCM, Vol 185, 2012) • High-risk environments for NTM in particular geographic areas of Hawai’i. (Adjemian, AJRCCM, Vol. 186, 2012) • Hawai’i also demonstrates the highest, national age-adjusted mortality rates from NTM-LD. (Mirsaeidi, 2014) CA: 191 AZ: 179 LA: MS: FL: 178 165 176 HI: 396 Current Lab Directions Hawai’i i.e., environmental water biofilms, soil, animal reservoirs, climate, etc….. Hawaiian Islands NTM lung disease i.e., host genetics/immunity, behaviors Honda, et al Frontiers in Microb, 2018 i.e., species pathogenicity Epidemiology of NTM lung disease in Hawai’i • Retrospective study, EMR database query (2005-13) • ~ 373,168 patient enrolled large healthcare system in Hawai’i – 1/3 of the state’s population • Period prevalence highest: 1) Oahu (153/100,000 cases); 2) Maui (91/100,000 cases), 3) Big Island (84/100,000 cases). No cases identified on other islands. • Highest among Japanese, Chinese, Korean, Vietnamese; lowest among Native Hawaiian/Other Pacific Islanders. 59.67% MAC 17.90% M. abscessus complex 22.43% M. fortuitum group Adjemian, et al, EID, 2017 Total=486 clinical isolates NTM species in respiratory specimens from Hawai’i n = 140 Oahu isolates (2018) 2.0% M. porcinum 2.7% M. avium 3.4% M. intracellulare 4.7% M. fortuitum 6.7% M. abscessus 18.1% M. massiliense 51.7% M. chimaera M. arosiense M. kubicae M. yongonense M. parascrofulaceum M. timonense M. senegalense M. bolletii M. simiae M. phocaicum First discoveries of NTM in Hawai’i households, 2012 75 households samples 172 household plumbing biofilms and soil No M. avium identified. M. intracellulare was very rare. Honda, et al, PLOS Neg Trop Disease, 2016 Hawai’i 2018 environmental samples ~ 1,500 new samples Analyses of the first 2012 219 new samples Households 37% 63% Household Non household Kauai – HH=83% (5/6) vs Non-HH=21% (6/28) Oahu– HH=90% (10/11) vs Non-HH=32% (18/57) Maui – HH=75% (3/4) vs Non-HH=23% (5/22) Hawai’i Island – HH=73% (8/11) vs Non-HH=92% (12/13) NTM recovery by island, island, by 2018 recovery NTM Novel NTM 50 youngest M. phocaicum 25 Hawai’i M. neoaurum d M. mucogenicum e r Island e M. iranicum v 20 40 s o M. immunogenum e l c e s e p g M. gordonae e r l a m p s M. gilvum d 15 a e Maui n i m s a M. conceptionense c l a s s 30 e s I M. canariasense o p s p s 10 M. arceuilense o f p M o Oahu M. wolinskyi T r M e N M. timonense T b 5 20 f N M. simiae o m f u Environmental species diversityn M. porcinum o N o Kauai i t M. intracellulare % 0 r o i M. fortuitum s e a e e e e e e e p u a m r m m m m m m a a s y s s s m m r M 10 s n u e u u u u u u n i n k n n n u u a T n a c it v c n c s r i l N o M. chimaera s o i i l i i o m e e e e v u e l a u i e i n in il s n u a l l r c e rc im t g n g n rd s l a a l e h h c r . ra o e . o o u i io o . e v s o o o g o e r t c P b c p c h f M i n g M im w c a e M a o M. chelonae a . u o . t . r p n r N . M p M c . a n e . t M M . M m u M M . a c M in M M m M c n . M. avium im . M . o . M c M M M . M. abscessus M 0 Kauai Oahu Maui Hawai'i Are all showerheads hot spots for NTM? Household showerhead biofilms Beach showerhead biofilms 53% (23/43) NTM positive 20% (10/50) NTM positive Total # showerheads tested (n=93) d e 4 r e v o c e r 3 s e i c e p s 2 • M M. avium T N f M. avium o 1 r e absent from the 2012 Hawai’ib study m u N 0 e a e m a r r M iu n e la T v o a u N discovereda l min Hawai’ill l streams . e i e e h h c v M c c a o . r N M t M in • . M 2018 streams were NTM positive. - 75% (6/8) samples collected from Oahu Oahu stream biofilms Interim summary A study within the study M. gilvum M. gordonae M.
Load more

Recommended publications
  • Extracellular Traps Released by Antimicrobial TH17 Cells Contribute to Host Defense
    Extracellular traps released by antimicrobial TH17 cells contribute to host defense George W. Agak, … , Matteo Pellegrini, Robert L. Modlin J Clin Invest. 2020. https://doi.org/10.1172/JCI141594. Research In-Press Preview Immunology TH17 cell subpopulations have been defined that contribute to inflammation and homeostasis, yet the characteristics of TH17 cells that contribute to host defense against infection are not clear. To elucidate the antimicrobial machinery of the TH17 subset, we studied the response to Cutibacterium acnes, a skin commensal that is resistant to IL-26, the only known TH17 secreted protein with direct antimicrobial activity. We generated C. acnes-specific antimicrobial TH17 clones (AMTH17) with varying antimicrobial activity against C. acnes, which we correlated by RNA-seq to the expression of transcripts encoding proteins that contribute to antimicrobial activity. Additionally, we validated that AMTH17-mediated killing of C. acnes as well as bacterial pathogens, was dependent on the secretion of granulysin, granzyme B, perforin and histone H2B. We found that AMTH17s can release fibrous structures composed of DNA decorated with the histone H2B that entangle C. acnes that we call T cell extracellular traps (TETs). Within acne lesions, H2B and IL-17 colocalized in CD4+ T cells, in proximity to TETs in the extracellular space composed of DNA decorated with H2B. This study identifies a functionally distinct subpopulation of TH17 cells with an ability to form TETs containing secreted antimicrobial proteins that capture and kill bacteria. Find the latest version: https://jci.me/141594/pdf Extracellular traps released by antimicrobial TH17 cells contribute to host defense George W.
    [Show full text]
  • Pdfs/ Ommended That Initial Cultures Focus on Common Pathogens, Pscmanual/9Pscssicurrent.Pdf)
    Clinical Infectious Diseases IDSA GUIDELINE A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2018 Update by the Infectious Diseases Society of America and the American Society for Microbiologya J. Michael Miller,1 Matthew J. Binnicker,2 Sheldon Campbell,3 Karen C. Carroll,4 Kimberle C. Chapin,5 Peter H. Gilligan,6 Mark D. Gonzalez,7 Robert C. Jerris,7 Sue C. Kehl,8 Robin Patel,2 Bobbi S. Pritt,2 Sandra S. Richter,9 Barbara Robinson-Dunn,10 Joseph D. Schwartzman,11 James W. Snyder,12 Sam Telford III,13 Elitza S. Theel,2 Richard B. Thomson Jr,14 Melvin P. Weinstein,15 and Joseph D. Yao2 1Microbiology Technical Services, LLC, Dunwoody, Georgia; 2Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota; 3Yale University School of Medicine, New Haven, Connecticut; 4Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland; 5Department of Pathology, Rhode Island Hospital, Providence; 6Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill; 7Department of Pathology, Children’s Healthcare of Atlanta, Georgia; 8Medical College of Wisconsin, Milwaukee; 9Department of Laboratory Medicine, Cleveland Clinic, Ohio; 10Department of Pathology and Laboratory Medicine, Beaumont Health, Royal Oak, Michigan; 11Dartmouth- Hitchcock Medical Center, Lebanon, New Hampshire; 12Department of Pathology and Laboratory Medicine, University of Louisville, Kentucky; 13Department of Infectious Disease and Global Health, Tufts University, North Grafton, Massachusetts; 14Department of Pathology and Laboratory Medicine, NorthShore University HealthSystem, Evanston, Illinois; and 15Departments of Medicine and Pathology & Laboratory Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey Contents Introduction and Executive Summary I.
    [Show full text]
  • Are There Good Models of Sarcoidosis?”
    Journal of Clinical Medicine Review Models Contribution to the Understanding of Sarcoidosis Pathogenesis: “Are There Good Models of Sarcoidosis?” Valérie Besnard 1,* and Florence Jeny 1,2 1 UMR 1272, Hypoxie & Poumon, Université Sorbonne Paris Nord, 1 rue de Chablis, 93017 Bobigny, France; fl[email protected] 2 AP-HP, Hôpital Avicenne, Service de Pneumologie, 93017 Bobigny, France * Correspondence: [email protected]; Tel.: +33-148-388-877; Fax: +33-148-388-924 Received: 8 July 2020; Accepted: 27 July 2020; Published: 31 July 2020 Abstract: Sarcoidosis is a systemic, granulomatous, and noninfectious disease of unknown etiology. The clinical heterogeneity of the disease (targeted tissue(s), course of the disease, and therapy response) supports the idea that a multiplicity of trigger antigens may be involved. The pathogenesis of sarcoidosis is not yet completely understood, although in recent years, considerable efforts were put to develop novel experimental research models of sarcoidosis. In particular, sarcoidosis patient cells were used within in vitro 3D models to study their characteristics compared to control patients. Likewise, a series of transgenic mouse models were developed to highlight the role of particular signaling pathways in granuloma formation and persistence. The purpose of this review is to put in perspective the contributions of the most recent models in the understanding of sarcoidosis. Keywords: sarcoidosis; models; macrophage; lung; granuloma 1. Introduction Sarcoidosis is a systemic disease of unknown etiology that is characterized by the formation of immune granulomas in different organs, mainly the lungs, the lymphatic system, the skin, the eye, and the heart [1]. The diagnosis consists of the association of compatible clinical, biological, and radiological signs, the histological demonstration of a granuloma characteristic of sarcoidosis, and the elimination of other causes of granulomatosis [2].
    [Show full text]
  • (Formerly Proprionibacterium Acnes) and Shoulder Surgery
    Cutibacterium acnes (formerly Proprionibacterium acnes) and Shoulder Surgery Marlee J. Elston BA; John P. Dupaix MD; Maria I. Opanova MBBS; and Robert E. Atkinson MD Abstract longer durations of culture, have been positive at higher levels for C. acnes at the time of revision ranging from 16% to 70%4,7,8 Infection is a rare but serious complication of shoulder arthroplasty. The most with the most common estimates around 50%-60%.4,8,9 In one prevalent cause of patient infections is Cutibacterium acnes (formerly Propri- study, the total infection rate was 1.9% with 89% caused by onibacterium acnes), a commensal skin bacterial species. Its presentation C. acnes.10 Similarly, in a study of deep infection after rotator is often non-specific and can occur long after shoulder arthroplasty, leading to delay in diagnosis. This bacterium is difficult to culture, typically taking 14 cuff injury, C. acnes was found to be the most prevalent cause 11 to 17 days for a positive culture and often does not exhibit abnormal results of infection, causing 51% of the post-surgical infection cases. on a standard laboratory workup for infection (eg, ESR, CRP, and synovial WBC count). Male patients are at particularly high-risk due to having a greater number of sebaceous follicles than females. While it is difficult to diagnose, Cutibacterium acnes Biology early diagnosis can lead to decreased morbidity, appropriate treatment, and improved clinical outcomes. Current options for treatment include antibiotics, First described by Paul Gerson Unna in 1865, C. acnes is a one stage implant exchange, or two stage implant exchange, although suc- cess rates of each are not currently well described.
    [Show full text]
  • Immunohistochemical Detection of Potential Microbial Antigens in Granulomas in the Diagnosis of Sarcoidosis
    Journal of Clinical Medicine Review Immunohistochemical Detection of Potential Microbial Antigens in Granulomas in the Diagnosis of Sarcoidosis Tetsuo Yamaguchi 1,2, Ulrich Costabel 3, Andrew McDowell 4 , Josune Guzman 5, Keisuke Uchida 1, Kenichi Ohashi 1 and Yoshinobu Eishi 1,* 1 Department of Human Pathology, Graduate School and Faculty of Medicine, Tokyo Medical and Dental University, Tokyo 113-8519, Japan; [email protected] (T.Y.); [email protected] (K.U.); [email protected] (K.O.) 2 Department of Pulmonology, Shinjuku Tsurukame Clinic, Tokyo 151-0053, Japan 3 Department of Pneumology, Ruhrlandklinik, Medical Faculty, University of Duisburg-Essen, 45239 Essen, Germany; [email protected] 4 Nutrition Innovation Centre for Food and Health (NICHE), School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UK; [email protected] 5 Department of General and Experimental Pathology, Ruhr University, 44801 Bochum, Germany; [email protected] * Correspondence: [email protected]; Tel.: +81-90-3332-0948 Abstract: Sarcoidosis may have more than a single causative agent, including infectious and non- infectious agents. Among the potential infectious causes of sarcoidosis, Mycobacterium tuberculosis and Propionibacterium acnes are the most likely microorganisms. Potential latent infection by both microorganisms complicates the findings of molecular and immunologic studies. Immune responses to potential infectious agents of sarcoidosis should be considered together with the microorganisms Citation: Yamaguchi, T.; Costabel, U.; detected in sarcoid granulomas, because immunologic reactivities to infectious agents reflect current McDowell, A.; Guzman, J.; Uchida, K.; Ohashi, K.; Eishi, Y. and past infection, including latent infection unrelated to the cause of the granuloma formation.
    [Show full text]
  • Prosthetic Joint Infection Diagnosis Using Conventional Methods
    11/5/2018 Prosthetic Joint Infection Diagnosis Using Conventional Methods HOT TOPIC / 2018 ©MFMER Presenter: Robin Patel, M.D. Professor of Medicine and Microbiology Chair, Division of Clinical Microbiology and the Elizabeth P. and Robert E. Allen Professor of Individualized Medicine Department of Laboratory Medicine and Pathology at Mayo Clinic, Rochester, Minnesota ©MFMER 1 11/5/2018 Disclosures • Dr. Robin Patel has a US patent for a method and an apparatus for sonication, but has foregone her right to personally receive royalties. Funding • National Institutes of Health • Department of Defense • National Science Foundation ©MFMER Total Hip and Knee Replacement Procedures United States1 Total knee Total hip Year ©MFMER 2 11/5/2018 ©MFMER Prosthetic Hip and Knee Infections: United States2 2001‐2020 ©MFMER 3 11/5/2018 Surgical Management of Prosthetic Hip or Knee Infection3 Reprinted with permission from Massachusetts Medical Society. ©MFMER Prosthetic Joint Infection Microbiology4 Hip and Knee Hip Knee Shoulder Elbow All time periods Early Number of joints 2435 637 1979 1427 199 110 Staphylococcus aureus 27 38 13 23 18 42 Coagulase negative staphylococci 27 22 30 23 41 41 Streptococcus species 846644 Enterococcus species 310223 0 Aerobic gram negative bacilli 92475107 Anaerobic bacteria 4395 Cutibacterium acnes 24 1 Other anaerobes 30 Culture negative 14 10 7 11 15 5 Polymicrobial 15 31 14 12 16 3 Other 3 ©MFMER 4 11/5/2018 Unusual Causes of Prosthetic Joint Infection5 Actinomyces israelii Granulicatella adiacens Aspergillus fumigatus
    [Show full text]
  • Short Chain Fatty Acids Produced by Cutibacterium Acnes Inhibit Biofilm
    www.nature.com/scientificreports OPEN Short chain fatty acids produced by Cutibacterium acnes inhibit bioflm formation by Staphylococcus epidermidis Kouki Nakamura 1, Alan M. O’Neill 1, Michael R. Williams 1, Laura Cau 1,2, Teruaki Nakatsuji 1, Alexander R. Horswill 3 & Richard L. Gallo 1* Bioflm formation by bacterial pathogens is associated with numerous human diseases and can confer resistance to both antibiotics and host defenses. Many strains of Staphylococcus epidermidis are capable of forming bioflms and are important human pathogens. Since S. epidermidis coexists with abundant Cutibacteria acnes on healthy human skin and does not typically form a bioflm in this environment, we hypothesized that C. acnes may infuence bioflm formation of S. epidermidis. Culture supernatants from C. acnes and other species of Cutibacteria inhibited S. epidermidis but did not inhibit bioflms by Pseudomonas aeruginosa or Bacillus subtilis, and inhibited bioflms by S. aureus to a lesser extent. Bioflm inhibitory activity exhibited chemical properties of short chain fatty acids known to be produced from C. acnes. The addition of the pure short chain fatty acids propionic, isobutyric or isovaleric acid to S. epidermidis inhibited bioflm formation and, similarly to C. acnes supernatant, reduced polysaccharide synthesis by S. epidermidis. Both short chain fatty acids and C. acnes culture supernatant also increased sensitivity of S. epidermidis to antibiotic killing under bioflm-forming conditions. These observations suggest the presence of C. acnes in a diverse microbial community with S. epidermidis can be benefcial to the host and demonstrates that short chain fatty acids may be useful to limit formation of a bioflm by S.
    [Show full text]
  • Cutibacterium Acnes As an Opportunistic Pathogen: an Update of Its Virulence-Associated Factors
    microorganisms Review Cutibacterium acnes as an Opportunistic Pathogen: An Update of Its Virulence-Associated Factors Constance Mayslich 1, Philippe Alain Grange 1,2 and Nicolas Dupin 1,2,* 1 NSERM Institut Cochin, INSERM U1016-CNRS UMR8104, Equipe de Biologie Cutanée, Université de Paris, 75014 Paris, France; [email protected] (C.M.); [email protected] (P.A.G.) 2 Service de Dermatologie-Vénéréologie, Groupe Hospitalier APHP.5, CNR IST Bactériennes—Laboratoire Associé Syphilis, 75014 Paris, France * Correspondence: [email protected]; Tel.: +33-158-411-849; Fax: +33-158-411-675 Abstract: Cutibacterium acnes is a member of the skin microbiota found predominantly in regions rich in sebaceous glands. It is involved in maintaining healthy skin and has long been considered a commensal bacterium. Its involvement in various infections has led to its emergence as an opportunist pathogen. Interactions between C. acnes and the human host, including the human skin microbiota, promote the selection of C. acnes strains capable of producing several virulence factors that increase inflammatory capability. This pathogenic property may be related to many infectious mechanisms, such as an ability to form biofilms and the expression of putative virulence factors capable of triggering host immune responses or enabling C. acnes to adapt to its environment. During the past decade, many studies have identified and characterized several putative virulence factors potentially involved in the pathogenicity of this bacterium. These virulence factors are involved in bacterial attachment to target cells, polysaccharide-based biofilm synthesis, molecular structures mediating inflammation, and the enzymatic degradation of host tissues. C. acnes, like other skin-associated Citation: Mayslich, C.; Grange, P.A.; bacteria, can colonize various ecological niches other than skin.
    [Show full text]
  • VITEK® MS Microbiology Powered by Mass Spectrometry DELIVER ACTIONABLE RESULTS to CLINICIANS to SUPPORT INFORMED TREATMENT DECISIONS
    VITEK® MS Microbiology Powered by Mass Spectrometry DELIVER ACTIONABLE RESULTS TO CLINICIANS TO SUPPORT INFORMED TREATMENT DECISIONS. Fast and actionable organism identification provides clinicians with valuable diagnostic information that helps them tailor antimicrobial therapy. Incorporating fast identification and AST* with stewardship interventions has been shown to reduce time to appropriate therapy and to reduce hospital length of stay.1 • Safe and effective inactivation and extraction protocols offer excellent performance for identification of pathogenic microorganisms • Easy workflow with convenient, prepackaged reagent kits • In-lab solution to save time and costs compared to sending out tests or using other methods *Antimicrobial Susceptibility Testing TRULY INTEGRATED ID & AST SETUP Simple, step-by-step guided slide preparation for ID and connection with AST using the on-screen VITEK MS Prep Station. SIMPLE SPOTTING Easy sample preparation step of spotting organism onto slide and applying sample matrix for bacteria or matrix plus formic acid for yeasts. FLEXIBLE SAMPLE LOADING VITEK MS carrier can be loaded with up to four prepared slides and introduced into the instrument. With 48 sample spots per target slide, 192 isolates can be tested per run. References 1. Cavalieri SJ, Kwon S, Vivekanandan R, et al. Effect of antimicrobial stewardship with rapid MALDI-TOF identification and VITEK 4. Dunne WMJ, Doing K, Miller E, et al. Rapid Inactivation of Mycobacterium and Nocardia species before identification using 2 antimicrobial susceptibility testing on hospitalization outcome. Diagn Microbiol Infec Dis. 2019. http://doi.org/10.1016/j. Matrix-Assisted Laser Desorption Ionization-Time of Flight mass spectrometry. J Clin Microbiol. 2014;52:3654-3659.
    [Show full text]
  • Review Memorandum
    510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K181663 B. Purpose for Submission: To obtain clearance for the ePlex Blood Culture Identification Gram-Positive (BCID-GP) Panel C. Measurand: Bacillus cereus group, Bacillus subtilis group, Corynebacterium, Cutibacterium acnes (P. acnes), Enterococcus, Enterococcus faecalis, Enterococcus faecium, Lactobacillus, Listeria, Listeria monocytogenes, Micrococcus, Staphylococcus, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus lugdunensis, Streptococcus, Streptococcus agalactiae (GBS), Streptococcus anginosus group, Streptococcus pneumoniae, Streptococcus pyogenes (GAS), mecA, mecC, vanA and vanB. D. Type of Test: A multiplexed nucleic acid-based test intended for use with the GenMark’s ePlex instrument for the qualitative in vitro detection and identification of multiple bacterial and yeast nucleic acids and select genetic determinants of antimicrobial resistance. The BCID-GP assay is performed directly on positive blood culture samples that demonstrate the presence of organisms as determined by Gram stain. E. Applicant: GenMark Diagnostics, Incorporated F. Proprietary and Established Names: ePlex Blood Culture Identification Gram-Positive (BCID-GP) Panel G. Regulatory Information: 1. Regulation section: 21 CFR 866.3365 - Multiplex Nucleic Acid Assay for Identification of Microorganisms and Resistance Markers from Positive Blood Cultures 2. Classification: Class II 3. Product codes: PAM, PEN, PEO 4. Panel: 83 (Microbiology) H. Intended Use: 1. Intended use(s): The GenMark ePlex Blood Culture Identification Gram-Positive (BCID-GP) Panel is a qualitative nucleic acid multiplex in vitro diagnostic test intended for use on GenMark’s ePlex Instrument for simultaneous qualitative detection and identification of multiple potentially pathogenic gram-positive bacterial organisms and select determinants associated with antimicrobial resistance in positive blood culture.
    [Show full text]
  • Clinical and Genomic Features of Corynebacterium Macginleyi-Associated Infectious Keratitis
    www.nature.com/scientificreports OPEN Clinical and genomic features of Corynebacterium macginleyi‑associated infectious keratitis Susanna Sagerfors1*, Anja Poehlein2, Mastaneh Afshar3, Birgitta Ejdervik Lindblad1, Holger Brüggemann3 & Bo Söderquist4 Infectious keratitis is a potentially sight threatening ophthalmological emergency. Contact lens wear is a common risk factor. Diagnostic advances such as MALDI‑TOF MS provides new insights into the spectrum of corneal pathogens and on microbes previously considered as commensals. Corynebacterium macginleyi was described in 1995, and in 2018, the genomic features of three isolates were reported after whole‑genome sequencing. Here we describe the clinical characteristics of patients with infectious keratitis (n = 29) presumably caused by Corynebacterium macginleyi, and analyze the genomic features of C. macginleyi (n = 22) isolated from the corneal ulcers of these patients. The disease course was uneventful apart from minor interventions such as corneal cross‑ linking and amniotic membrane transplant. Genome sequencing and comparison revealed a highly conserved core genome of C. macginleyi. Based on the analyses of single nucleotide polymorphisms, the population could be divided into two main clades that also difered in a few clade‑specifc genomic islands. Patients infected with an isolate belonging to the minor clade (n = 7) presented a more severe disease. Comparisons with other corynebacterial species clearly separated C. macginleyi. C. macginleyi may be considered a corneal pathogen; genomic analysis provided insights into its population structure and disease‑causing potential. Corynebacterium macginleyi, a slow-growing, lipid-requiring, Gram-positive, facultative anaerobic rod named afer Kenneth McGinley, was frst described by Riegel et al.1. All three strains of C. macginleyi covered in that report were isolated from human eyes, and from a phylogenetic perspective showed most resemblance to Corynebacterium accolens.
    [Show full text]
  • Abnormal Uterine Bleeding Acute and Chronic Cognitive Diseases
    Abnormal Uterine Bleeding Would you be able to obtain repeat endometrial bx after inserting IUD Slide 18 Yes How long would would you treat AUB with medroxy-progesterone, also when stopping the therapy does it need to be tapered Clinically - I treat for three months. The data is VERY limited on duration. choice for young women with hirsutism who do not want to become pregnant. Spironolactone, in daily doses of 50-200 mg, blocks androgen receptors. Spironolactone also decreases testosterone production, making it additionally effective for hirsutism. Sexually active women taking spironolactone should ensure that contraceptive measures are adequate. In some cases, spironolactone can be combined with an OC for added effect on the hirsutism. With current systemic therapies for hirsutism, 6 months to a year of therapy is usually required before results are noticeable. Even then, only approximately one half to three quarters of patients show improvement. The problem may lie partially in the nature of the hair follicle, which persists for 6 months to a year even after androgen levels have been normalized. Ineffectiveness may also be due to the inability of treatment to completely normalize elevated tissue dihydrotestosterone levels. Newer therapies directed at inhibition of 5-alpha-reductase or blockade of the androgen receptor may improve the ability to treat what is the dose for spironolactone for hirsutism patients. Acute and Chronic Cognitive Diseases Common Issues in the Elderly I would be most appropriate because they wouldn't be rushed to further intervention. Certainly, if there are other red flags on exam or sx don't improve with conservative management, imaging is an appropriate next For lumbar stenosis, why would you not do an MRI first step is post prandial hypotension common in younger people too Not as common because younger people typically have better overall blood flow For lumbar stenosis, what if conservative therapy (i.e.
    [Show full text]